The process products are sought-after compounds for the preparation of a multitude of subsequent products, for example for the preparation of anti-allergic medicaments such as 4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha,alpha-dimethylphenylacetic acid, referred to below as fexofenadine (U.S. Pat. No. 4,254,129). The central synthetic building block in the preparation of fexofenadine is 2-[4-(4-chlorobutanoyl)phenyl]-2-methylpropionic acid.
Known processes for preparing 2-[4-(4-chlorobutanoyl)phenyl]-2-methyl-propionic acid (EP0703902, WO95/00482, U.S. Pat. No. 4,254,129, WO97/23213, WO97/22344, WO95/00480, WO93/21156, U.S. Pat. No. 4,254,130, WO2003/000658) have a high number of stages and lead to p and m positional isomers which subsequently have to be separated from one another. In addition, the intermediates in the known processes often have to be purified by column chromatography, which complicates the synthesis of large amounts of substance in a pilot plant or on the production scale.
It has now been found that the disadvantages mentioned can be avoided by a short, efficient and isomer-free synthesis which also dispenses with costly and inconvenient purification steps such as column chromatography.
The object is achieved by carbonylating the compounds of the formula II with carbon monoxide in the presence of a superacid. In this way, the formation of positional isomers is prevented and the compounds of the formula (I) can be prepared in only 2 to 4 synthetic stages with high yield and purity.